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The production of reactive oxygen species (ROS) in a highly regulated fashion is a hallmark of members of the NADPH oxidase (Nox) family of enzymes. Nox enzymes are present in most eukaryotic groups such as the amebozoid, fungi, algae and plants, and animals, in which they are involved in seemingly diverse biological processes. However, a comprehensive survey of Nox functions throughout biology reveals common functional themes. Noxes are often activated in response to stressful conditions such as nutrient starvation, physical damage, or pathogen attack. Although the end result varies depending on the organism and tissue, Nox-produced ROS mediate the response to the adverse stimuli, such as innate immunity responses in plants and animals or cell differentiation in Dictyostelium, fungi, and plants. These responses involve ROS-mediated signaling mechanisms occurring at intracellular or cell-to-cell …